Taxol and Related Compounds Anticancer Drugs

Why does Viagra work this way Let us look at Fig. 7.5. Both cGMP and Viagra have similar structural features as indicated by the colored boxes. Because of this similarity, they bind to the same site of the enzyme. The other drugs put on market in recent years, Cialis and Levitra (see Fig. 7.5), are also spedlic inhibitors of PDE5. 

National Cancer Institute (NCI) sponsored between 1958 and 1980 a number of projects in which more than 35,000 plant species were tested for anticancer activities. Monroe E. Wall and M. C. Wani of Research Triangle Institute obtained a ande extract from the bark of Pacific yew tree (Taxus brevifolia) in 1963, which they demonstrated to be very effective against a wide range of cancers, particularly ovarian and breast cancers. They named the agent Taxol. However, they did not apply for a patent for their discovery. It took several more years to figure out the structure of the compound (1971 see Fig. 7.6 for the structure). 

It turned out that yew trees not only of the Pacific coast but of other species contain a compound called 10-deacetylbaccatin III (see Fig. 7.6) this is a precursor of taxol. You see in Fig. 7.6 that taxol consists of two portions A and B, and that this precursor provides the portion A. Now, to make another compound starting with a simpler compound is called Chemical Synthesis, and this is what chemists excel at. Some people even say that this, chemical synthesis, is the only thing that is a proper chemistry. In this case, you have to add portion B on to the existing portion A. Robert A. Holton of Horida State University succeeded in synthesizing taxol from 10-deacetylbaccatin III. 

Bristol-Myers Squibb Company sold 1.6 bilhon worth taxol in 2000. Phyton, Inc. in Ithaca, New York, is developing a technology to produce taxol by plant cell fermentation and is now collaborating with Bristol-Myers Squibb. 

Meanwhile, on the other side of the Atlantic, French scientists were busy developing other derivatives of taxol. Scientists at the Institut de Chimie des Substances Naturelles, Universite Joseph Fourier, and at RhOne-Poulenc (a pharmaceutical company) have synthesized 40 or so taxol-like compounds and tested their effectiveness and found that taxotbre was the most potent. The structure of taxotere is shown in Fig. 7.6. It has a slightly different entity for portion B. This is chanically synthesized starting with 10-deacetylbaccatin HI, which they obtain from the leaves of yew bush, Taxus baccata. This compound was patented by Rhone-Poulenc. 

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